SUN-665 Meta-Analysis of Psychiatric and Quality of Life Outcomes in Patients With Obesity and Diabetes Treated With Glucagon-Like Peptide 1 Receptor Agonists

Abstract Disclosure: A.C. Pierret: None. Y. Mizuno: None. P. Saunders: None. E. Lim: None. R. De Giorgi: None. O.D. Howes: None. R.A. McCutcheon: None. B.M. McGowan: None. P. Sen Gupta: None. D. Smith: None. K. Ismail: None. T. Pillinger: None. Background and objective: Obesity and diabetes mellitus are associated with poorer mental health and reduced quality of life (QoL). Glucagon-like peptide 1 receptor agonists (GLP1-RAs) are treatments for these conditions; however, existing data are conflicting with regards to their effects on psychiatric outcomes. We aimed to meta-analyse psychiatric and QoL outcomes in randomised placebo-controlled trials of GLP1-RA treatment in patients with obesity and/or diabetes mellitus. Methods: We searched MEDLINE, Embase, PsycINFO, and CENTRAL databases until 24/06/2024. Double-blind placebo-controlled trials comparing GLP1-RA to placebo in adults with obesity and/or diabetes mellitus, reporting on psychiatric or QoL outcomes, were included. Random-effects meta-analysis was performed. Main outcomes were risk of psychiatric adverse events (serious and non-serious), change in mental health symptom severity, and QoL. Effect size measures were log risk ratios (log(RR)) and standardised mean differences (Hedges’ g). Random-effects meta-regression assessed the effects of change in weight and HbA1c during study period on outcomes. Results: 80 randomised controlled trials were included in the meta-analysis, including 107,860 patients. Mean age of participants was 60.1 (7.1) years, with 40.1% female. The population was T2DM in 62% of studies, obesity in 29%, and T1DM in 9%. Median treatment duration was 28 weeks (IQR 24-56 weeks). The most studied drugs were liraglutide (30%) and semaglutide (24.7%). There was no significant difference between GLP1-RA and placebo for risk of serious (log(RR)=-0.02 [95%CI -0.20-0.17], p=0.87) and non-serious (log(RR)=-0.03 [95%CI -0.21 - 0.16], p=0.76) psychiatric adverse events, or in depressive symptom change (g=0.02 [95%CI -0.51-0.55], p=0.94). GLP1-RA treatment was associated with improvements in restrained eating (g=0.35 [95%CI 0.13-0.57], p=0.002) and emotional eating behavior (g=0.32 [95%CI 0.11-0.54], p=0.003), and improvements in all QoL subdomains (mental health, physical health, diabetes-related and weight-related) (g=0.15-0.27, p<0.001 for all) compared to placebo. There was no association between change in mental health QoL with magnitude of weight- or HbA1c-change (p>0.05). There was a positive association between weight loss and change in both physical health QoL (z=-2.744, p=0.006) and weight-related QoL (z=-3.19, p=0.001). Discussion: In patients with obesity and/or diabetes mellitus, GLP1-RA treatment is not associated with increased risk of psychiatric adverse events or worsening depressive symptoms relative to placebo. It is associated with improvements in QoL (which is not entirely weight-related) and in eating behaviors. This provides reassurance regarding the psychiatric safety profile of GLP1-RAs and suggests concurrent improvement in mental health, in addition to their known physical health benefits. Presentation: Sunday, July 13, 2025